Turban J, Beckwith N, Reisner S, Keuroghlian A. Association Between Recalled Exposure to Gender Identity Conversion Efforts and Psychological Distress and Suicide Attempts Among Transgender Adults [Internet]. JAMA Psychiatry 2019;77(1):1-9. LinkAbstract

Importance  Gender identity conversion efforts (GICE) have been widely debated as potentially damaging treatment approaches for transgender persons. The association of GICE with mental health outcomes, however, remains largely unknown.

Objective  To evaluate associations between recalled exposure to GICE (by a secular or religious professional) and adult mental health outcomes.

Design, Setting, and Participants  In this cross-sectional study, a survey was distributed through community-based outreach to transgender adults residing in the United States, with representation from all 50 states, the District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas. Data collection occurred during 34 days between August 19 and September 21, 2015. Data analysis was performed from June 8, 2018, to January 2, 2019.

Exposure  Recalled exposure to GICE.

Main Outcomes and Measures  Severe psychological distress during the previous month, measured by the Kessler Psychological Distress Scale (defined as a score ≥13). Measures of suicidality during the previous year and lifetime, including ideation, attempts, and attempts requiring inpatient hospitalization.

Results  Of 27 715 transgender survey respondents (mean [SD] age, 31.2 [13.5] years), 11 857 (42.8%) were assigned male sex at birth. Among the 19 741 (71.3%) who had ever spoken to a professional about their gender identity, 3869 (19.6%; 95% CI, 18.7%-20.5%) reported exposure to GICE in their lifetime. Recalled lifetime exposure was associated with severe psychological distress during the previous month (adjusted odds ratio [aOR], 1.56; 95% CI, 1.09-2.24; P < .001) compared with non-GICE therapy. Associations were found between recalled lifetime exposure and higher odds of lifetime suicide attempts (aOR, 2.27; 95% CI, 1.60-3.24; P < .001) and recalled exposure before the age of 10 years and increased odds of lifetime suicide attempts (aOR, 4.15; 95% CI, 2.44-7.69; P < .001). No significant differences were found when comparing exposure to GICE by secular professionals vs religious advisors.

Conclusions and Relevance  The findings suggest that lifetime and childhood exposure to GICE are associated with adverse mental health outcomes in adulthood. These results support policy statements from several professional organizations that have discouraged this practice.

Praschan N, Beckwith N, McDowell M, Wininger B, Ivkovic A, Beach S. Poster 087 - Psychosis and Epilepsy in a 48-year-old Latina Woman Following Surgical Correction of a Tegmen Tympani Encephalocele [Internet]. Presented at ACLP in San Diego, CA 2019; LinkAbstract
Introduction: We present a patient who developed psychosis following correction of an encephalocele of the tegmen tympani, a thin aspect of the temporal bone separating the tympanic and cranial cavities. To our knowledge, there are no reports of psychosis following this surgery.

Case: At onset, BE was a 48-year-old Latina woman whose only psychiatric history had been depression and anxiety. She long struggled with idiopathic intracranial hypertension. She developed CSF otorrhea and underwent correction of an encephalocele, which involved a right temporal craniotomy. Within weeks, she experienced her first seizure, confirmed on EEG with right temporal slowing and spikes. She was prescribed levetiracetam and lamotrigine. Shortly thereafter, she developed persecutory delusions and tactile hallucinations. She was unsuccessfully treated in the community with olanzapine and psychotherapy. During an admission in 2017, her psychotic symptoms were found to have no EEG correlate. Levetiracetam was tapered with a plan to discontinue, and her illness responded to paliperidone. Unfortunately, levetiracetam was never tapered and she was prescribed olanzapine again in the community. She was ultimately referred to MGH psychiatry. In coordination with neurology, her levetiracetam was discontinued; lamotrigine was increased. She was prescribed risperidone, and after an admission due to nonadherence and underreporting symptoms, improved with medication, assisted by a visiting nurse.

Discussion: This case highlights the differential diagnosis of psychosis in a neurologically complex patient. This differential includes primary psychosis; substance-induced; psychoses associated with epilepsy (ictal, postictal, interictal psychoses); medication-induced; and psychosis from neurological injury. Given her age of onset and the prominence of tactile hallucinations, a primary psychotic disorder is unlikely. Stimulant-induced psychotic disorders, especially methamphetamine, are associated with paranoia and tactile hallucinations. However, there were no reports of substance use and her urine toxicologies were negative. Medication-induced psychosis, specifically levetiracetam, was a consideration, but her psychosis persisted months after discontinuation. Her psychotic symptoms do not occur in the ictal period nor in the days following, ruling out ictal and postictal psychoses. Interictal psychosis, a schizophrenia-like syndrome, occurs after years of controlled epilepsy. It is most likely that this illness resulted from neurosurgical injury. Supporting evidence for this hypothesis includes the temporal association with surgery and post-surgical MRI changes in right temporal lobe, lesions to which have resulted in psychosis in multiple case series in the literature. This case is also exemplary of Latinx values relevant to the therapeutic alliance, including respeto (deference to authority figures) and simpatia (preference for themes of positive valence).

Conclusion: The process of ruling out general medical conditions, medications, substances, and understanding the phenomenology of neuropsychiatric conditions is essential for treating such complex cases. An approach that favored interdisciplinary communication, appreciation of cultural values, and interventions beyond pharmacology resulted in a good clinical outcome.
Beckwith N, McDowell MJ, Reisner SL, Zaslow S, Weiss RD, Mayer KH, Keuroghlian AS. Psychiatric Epidemiology of Transgender and Nonbinary Adult Patients at an Urban Health Center [Internet]. LGBT Health 2019;6(2):51-61. LinkAbstract

Purpose: Transgender and nonbinary people have an increased burden of psychiatric problems compared with the general population. Data are needed to understand factors associated with psychiatric diagnoses, acuity in terms of suicide attempts and level-of-care escalation, and outpatient engagement among transgender and nonbinary adults.

Methods: We conducted a retrospective review of records from 201 transgender and nonbinary adults who presented for primary care at a health center. Regression models were fit to examine factors associated with psychiatric diagnoses, substance use disorders (SUDs), acuity, and outpatient behavioral health engagement.

Results: Male sex assignment at birth was associated with decreased odds of a psychiatric diagnosis (odds ratio [OR] 0.40, 95% confidence interval [CI]: 0.20–0.81). Increased odds of SUDs were associated with later hormone initiation (OR 1.04, 95% CI: 1.01–1.08) and suicide attempt (OR 5.79, 95% CI: 2.08–16.15). Increased odds of higher acuity were associated with alcohol use disorder (OR 31.54, 95% CI: 5.73–173.51), post-traumatic stress disorder (OR 18.14, 95% CI: 2.62–125.71), major depressive disorder (MDD) (OR 6.62, 95% CI: 1.72–25.44), and absence of psychiatrist integration into primary medical care (OR 4.52, 95% CI: 1.26–16.22). Increased odds of outpatient behavioral health engagement were associated with case management utilization (OR 10.73, 95% CI: 1.32–87.53), anxiety disorders (OR 15.84, 95% CI: 2.00–125.72), and MDD (OR 10.45, 95% CI: 2.28–47.98).

Conclusion: Psychiatric disorders were highly prevalent among transgender and nonbinary adult patients. Novel findings include associations of lack of psychiatrist integration into primary care with acuity and of case management utilization with outpatient behavioral health engagement.

Beckwith N, Reisner SL, Zaslow S, Mayer KH, Keuroghlian AS. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults [Internet]. Transgender Health 2017;2(1):156-164. LinkAbstract

Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults.

Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation.

Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist.

Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients.

Beckwith N, Jean-Baptiste M-L, Katz A. Waiting Room Education in a Community Health System: Provider Perceptions and Suggestions [Internet]. Journal of Community Health 2016; LinkAbstract

The increasing burden of chronic diseases in the United States presents a major challenge to the nation’s primary care systems, so improving the efficacy and efficiency of patient education is an important goal. Understanding the current perspectives, practices, and needs of primary care providers should guide innovation towards this end. As a part of the authors’ ongoing quality improvement work, a short internet survey was an effective method of enhancing this understanding in one health care system. With a response rate of 24.6 %, the survey revealed that primary care waiting rooms in the health system studied are not conceived of or used by providers as spaces to engage patients in health education. To change this, providers suggested using both printed and technological methods for delivering health information, primarily related to medications, diabetes, and healthy lifestyle practices. Common barriers to improvement cited by providers included diverse language and literacy backgrounds in the patient population, as well as difficulty sustaining change due to infrastructural and administrative barriers. These results suggest steps for development, implementation, and investigation of new educational interventions for patients in the local primary care context.

Abudayyeh O, Beckwith NMR, Frange A, Kumar J. Harvard Medical Student Review [Internet]. 2014; Link hmsr-issue-1.pdf hmsr-issue-2.pdf hmsr-issue-3.pdf hmsr-issue-4.pdf
Streeck H, Lu R, Beckwith N, Milazzo M, Liu M, Routy J-P, Little S, Jessen H, Kelleher AD, Hecht F, Sekaly R-P, Alter G, Heckerman D, Carrington M, Rosenberg ES, Altfeld M. Emergence of individual HIV-specific CD8 T cell responses during primary HIV-1 infection can determine long-term disease outcome [Internet]. Journal of Virology 2014; epub ahead of print LinkAbstract

Background. Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral setpoint have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1.

Methods. A total of 620 individuals with primary HIV-1 infection were screened by IFNγ Elispot for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months post initial presentation. The cohort was predominantly male(97%)Caucasian(83%) (Fiebig: II/III:[n=152], IV:[n=61], V:[n=277], VI:[n=87], nd:[n=23]). Longitudinal viral loads, CD4 count and time to ART were collected for all patients.

Results. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (p<0.0001). Both were significantly associated with HLA class I genotypes (p=0.0009). While neither the breadth nor magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses - but not others —significantly influenced the time to ART initiation.

Conclusions. Individual epitope-specific CD8 T cell responses are significantly contributing to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of their antiviral function.

IMPORTANCE Understanding which factors are involved in the control of HIV infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here we assessed in a cohort of over 600 individuals with acute and early HIV infection in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV to control of viremia and their impact on the overall course of disease progression.

Accepted-Blog. Interview with a Current Harvard Med Student: Shaping the Evolution of Humanity’s Health [Internet]. 2014; LinkAbstract

This interview is the latest in an blog series featuring interviews with medical school applicants and students, offering readers a behind-the-scenes look at top medical schools and the med school application process. And now, introducing Noor…

Abudayyeh O, Beckwith N, Frange A, Kumar J. Introducing the Harvard Medical Student Review [Internet]. Harvard Medical Student Review 2014;1(1):e1. Link introducinghmsr.pdf
Beckwith NMR. Redefining Suffering and Illness [Internet]. Harvard Medical Student Review 2014;1(1):e8. LinkAbstract

In order to nuance and reframe dialogues around healthcare, I introduce and define fundamental terms and concepts with the aid of anthropological and sociological literature, modifying and updating them as reason, need, and humanity require. I establish suffering as the experience of threat or damage to personhood, with illness as its manifestation. I then describe and distinguish two ways of attempting to manage health: caregiving, a moral exchange that sustains personhood for both provider and receiver; and biomedicine, an interpretive system that seeks mainly to govern pathophysiological disease. I briefly apply these concepts to highlight shortcomings within the current focus of the medical profession, and I invite continued engagement with these terms in order to bring closer to lived-experience our conceptualization of what is at stake.

Vaidya SA, Streeck H, Beckwith N, Ghebremichael M, Pereyra F, Kwon DS, Addo MM, Rychert J, Routy J-P, Jessen H, Kelleher AD, Hecht F, Sekaly R-P, Carrington M, Walker BD, Allen TM, Rosenberg ES, Altfeld M. Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection. Retrovirology 2013;10(1):139.Abstract
BACKGROUND: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). FINDINGS: Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint. CONCLUSIONS: The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.
Li R, Yu C, Jiang F, Gao L, Li J, Wang Y, Beckwith N, Yao L, Zhang J, Wu G. Overexpression of N-Myc Downstream-Regulated Gene 2 (NDRG2) Regulates the Proliferation and Invasion of Bladder Cancer Cells In Vitro and In Vivo. PLoS One 2013;8(10):e76689.Abstract
N-Myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor gene, which plays an important role in controlling tumor growth. The aim of this study was to investigate the expression of NDRG2 gene in bladder cancer (BC) tissues and several bladder cancer cell lines, and to seek its clinical and pathological significance. Ninety-seven bladder carcinoma and 15 normal bladder tissue sections were analyzed retrospectively with immunohistochemistry. The human bladder cancer cell line T24 was infected with LEN-NDRG2 or LEN-LacZ. The effects of NDRG2 overexpression on T24 cells and T24 nude mouse xenografts were measured via cell growth curves, tumor growth curves, flow cytometric analysis, western blot and Transwell assay. NDRG2 was highly expressed in normal bladder tissue, but absent or rarely expressed in cacinomatous tissues (χ(2)=8.761, p < 0.01). The NDRG2 level was negatively correlated with tumor grade and pathologic stage(r=-0.248, p < 0.05), as well as increased c-myc level (r=-0.454, p< 0.001). The expression of NDRG2 was low in the three BC cell lines. T24 cells infected with LEN-NDRG2 showed inhibition of proliferation both in vitro and in vivo, and NDRG2 overexpression can inhibit tumor growth and invasion in vitro.
Whiteman NK, Groen SC, Chevasco D, Bear A, Beckwith N, Gregory RT, Denoux C, Mammarella N, Ausubel FM, Pierce NE. Mining the plant–herbivore interface with a leafmining Drosophila of Arabidopsis [Internet]. Molecular Ecology 2011;20(5):995-1014. PubMedAbstract

Experimental infections of Arabidopsis thaliana (Arabidopsis) with genomically characterized plant pathogens such as Pseudomonas syringae have facilitated the dissection of canonical eukaryotic defence pathways and parasite virulence factors. Plants are also attacked by herbivorous insects, and the development of an ecologically relevant genetic model herbivore that feeds on Arabidopsis will enable the parallel dissection of host defence and reciprocal resistance pathways such as those involved in xenobiotic metabolism. An ideal candidate is Scaptomyza flava, a drosophilid fly whose leafmining larvae are true herbivores that can be found in nature feeding on Arabidopsis and other crucifers. Here, we describe the life cycle of S. flava on Arabidopsis and use multiple approaches to characterize the response of Arabidopsis to S. flava attack. Oviposition choice tests and growth performance assays on different Arabidopsis ecotypes, defence-related mutants, and hormone and chitin-treated plants revealed significant differences in host preference and variation in larval performance across Arabidopsis accessions. The jasmonate and glucosinolate pathways in Arabidopsis are important in mediating quantitative resistance against S. flava, and priming with jasmonate or chitin resulted in increased resistance. Expression of xenobiotic detoxification genes was reduced in S. flava larvae reared on Arabidopsis jasmonate signalling mutants and increased in plants pretreated with chitin. These results and future research directions are discussed in the context of developing a genetic model system to analyse insect-plant interactions.

Yu C, Wu G, Dang N, Zhang W, Zhang R, Yan W, Zhao Y, Gao L, Wang Y, Beckwith N, Yuan J, Yao L. Inhibition of N-myc downstream-regulated gene 2 In prostatic carcinoma [Internet]. Cancer Biology & Therapy 2011;12(4):304-313. PubMedAbstract

To study the expression of N-myc Downstream Regulated Gene-2 (NDRG2) in prostatic carcinoma (PCA) tissue and in different PCA cell lines, and to investigate its clinical and pathological implications, 144 PCA and benign prostatic hyperplasia (BPH) tissue sections were analyzed retrospectively with immunohistochemistry (S-P method). The expression levels of NDRG2 and c-Myc in prostate cell lines were detected through Western blot. The effects of adenovirus-mediated NDRG2 on PC3 cells and PC3 nude mouse xenografts was observed through cell growth curves, tumor growth curves, flow cytometry (FCM), transmission electron microscopy (TEM) and TUNEL staining. The NDRG2 gene was highly expressed in BPH tissues, but not in carcinomatous ones (χ(2)=25.98, p < 0.001). Furthermore, positive expression of NDRG2 was negatively correlated with the Gleason score (r = -0.445, p< 0.001) and the c-myc level (r = -0.311, p < 0.001). However, positive expression of NDRG2 was not correlated with pTNM tumor stages or the serum concentration of prostate-specific antigen (PSA) (p > 0.05). The expression of the NDRG2 genes was low in the three PCA cell lines. PC3 cells infected by pAD-cmv-NDRG2 showed inhibition of proliferation both in vitro and vivo. To sum up, NDRG2 may be involved in the carcinogenesis and progression of PCA. Moreover, adenovirus-mediated NDRG2 can suppress the proliferation of PC3 cells significantly both in vitro and in vivo. These results indicate that NDRG2 may become a new target gene for PCA diagnosis and therapy.

Zhang S, Beckwith N. On the move [Internet]. The Harvard Undergraduate Research Journal 2009;2(2):3, 6-9. View
Beckwith N. Photojournalism oeuvre for The Harvard Crimson, 2009-2012 [Internet]. 2009; View
Beckwith N. The Biodiversity of Borneo [Internet]. The Harvard Undergraduate Research Journal 2008;1(2):cover, 6-7. View 6-7.pdf fall08_cover.jpg